- The International Advisory Committee on Clinical Trials in MS held a workshop to review current knowledge on MS management in older people.
- Normal ageing and other diseases make the diagnosis, monitoring and treatment of MS more complex in older age.
- Careful clinical and medication management, a brain-healthy lifestyle, and collection of more specific data for this group were recommended.
While MS usually presents in early to mid-adulthood, improvements in healthcare mean that around half of people currently living with MS are 50 years of age or older. However, diagnosis, treatment and management of MS become more complex as people age, amidst the normal age-related changes in the brain, immune and other body systems, as well as the increased risk of developing other diseases.
A workshop on ageing and MS was recently convened by the International Advisory Committee on Clinical Trials (IACCT) in MS. Led by Australian neurologist and researcher, Associate Professor Anneke van der Walt, the expert group reviewed the current evidence, identified knowledge gaps and developed recommendations to improve management of MS in people aged 50 and older, The outcomes of this workshop were published in Nature Reviews Neurology as a consensus statement.
Ageing and MS disease processes
With normal ageing, there is a weakening of the immune system, but at the same time, a more inflammatory state develops. These changes can exacerbate MS disease processes and accelerate nerve damage. In addition, sex hormones, which would normally have a protective effect on the nerves, decline with age, further contributing to nerve damage.
However, these changes can be offset by the brain and spinal cord “reserve”. Reserve is the capacity to maintain function in the face of disease. It includes a fixed component, such as the size and number of nerve cells, and also “functional reserve”, which reflects the capacity to maintain physical and cognitive (thinking and memory) function despite damage.
Importantly, this might be strengthened by lifestyle choices to improve brain health. These include the use of MS disease-modifying therapies (DMTs), mental stimulation, keeping a healthy weight and diet, exercise, and not smoking. These all help build functional reserve to protect against MS disability progression with age.
MS diagnosis and prognosis with ageing
MS onset can look different in older people, with spinal cord changes more likely, optic nerve inflammation less common, and progressive disease from the start more likely (40%, compared to 10% for adult-onset MS).
It can also be more difficult to distinguish MS because of overlapping features with other age-related conditions. One example is white-matter lesions on MRI, also seen in cerebral vascular disease, migraine, or with the use of immune therapies for other diseases, such as some cancer drugs. These complexities can result in delayed diagnosis, so rigorous clinical review is important to help avoid these delays. The new diagnostic criteria for MS, released in 2025, include additional safeguards to help diagnose older people.
Cognitive difficulties are more common in older people with MS. MS-related changes include changes in verbal learning, executive functioning and processing speed, but more research is needed to understand these changes in older people. These differ from the cognitive changes seen in Alzheimer’s disease and dementia disorders that affect memory.
The presence of other health conditions in older people with MS can affect MS activity and a person’s prognosis. High blood pressure, high blood lipids, anxiety and depression are the most common of these and are associated with worse MS outcomes. Careful monitoring and management of these conditions gives the potential to improve MS outcomes.
Ageing and disease monitoring
Similar to the issues around MS diagnosis, there are changes with age that can complicate MS monitoring. Brain shrinkage, lesions on MRI, eye changes and increased blood markers of inflammation and nerve degeneration all increase with normal ageing.
Perhaps the clearest illustration of this is the system used to score disability in MS, the Expanded Disability Status Scale (EDSS), which ranges from 0 to 10, with 0 indicating no disability. In a recent study of people without MS aged ≥55 years, no one had an EDSS score of 0, and the average score was 3, defined as mild to moderate established neurological impairment.
A similar situation is found with cognitive testing of older people.
Specific reference ranges have been and are being developed for older people. These will help tease out the effects of MS from the effects of normal ageing to help with MS monitoring.
Treatment of MS in old age
Disease-modifying therapies
Highly effective DMTs for MS have been available for over 20 years and can slow progression when used early. While clinical trials of these therapies have typically excluded people aged ≥50–55 years, data from registry-based and other industry studies provide some insights.
These studies have shown that DMTs continue to provide benefits in older people with MS and those with late-onset MS, particularly in reducing relapses and MRI lesion activity. Notably, high-efficacy treatments have produced the best outcomes.
Whether DMTs can slow disability worsening in older people with MS and late-onset MS is still unclear.
Other health conditions
Other health conditions increase the complexity and uncertainty of MS treatment in older people with MS. They can reduce tolerance to MS DMTs, meaning people don’t always stay on them, leading to worse outcomes. There is also limited data on the safety of using MS therapies in conjunction with immune medications (e.g. for cancer), or the safety of long-term use in this group.
For people receiving DMTs for MS, the risk of serious infections is increased in those with advanced disability and prolonged exposure to immunosuppressive drugs. This highlights the importance of keeping vaccines up-to-date for older people with MS on these therapies.
Holistic treatment
Non-medication and holistic treatments are essential for any older person, and even more so in people living with MS who experience accelerated ageing. Adopting a brain-healthy lifestyle to minimise the effects of ageing and build cognitive and physical reserve is key.
As an example, exercise has anti-inflammatory effects on the immune system, and preserves brain volume and brain structure at the microscopic level in people with MS.
Protection and regeneration of nerves
There are many new drugs in development to stop or repair nerve degeneration in MS. Natural repair and regrowth of myelin is known to be less effective with age, so access to these treatments will be especially important for this group. Of particular interest are treatments that may have both remyelinating and anti-ageing properties, such as metformin, being tested in the PLATYPUS-OCTOPUS and other clinical trials.
Stopping MS therapies in older age
As people age, relapses and MRI lesions are less frequent, and MS is more often progressive. The benefit of DMTs for progressive disease is unclear, raising concerns about continuing medication unnecessarily.
Retrospective studies suggest that stopping therapy seems relatively safe for people aged ≥60 years with a long disease duration (>15 years) and stable disease (no relapses or new MRI lesions for at least 3–5 years).
A Phase IV clinical trial known as DISCOMS found that people with MS who were >55 years and had stable disease (no relapse for 5 years) on low-efficacy DMTs could safely stop treatment, although a small proportion (16 of 131 participants) did experience new or expanding brain MRI lesions.
In contrast, a French National MS Registry study that included younger people living with MS (average age 54.7 years) with higher disability levels (median EDSS = 4.0) found that stopping therapies that reduce immune cell movement between tissues in the body (natalizumab and fingolimod) after the age of 50 years increased the risk of relapses even if the disease was stable before discontinuation. This risk was not increased for B-cell depleting therapies (eg ocrelizumab).
These studies show that stopping treatment at an older age is not without risk, and special care should be taken when stopping drugs that prevent immune cells from moving around the body.
More research is needed to clarify the ideal recommendations for stopping MS treatment at an older age.
What does this mean for people with MS and MS research?
There are added considerations for MS management in older age, so clear communication between different specialists in the healthcare team is important. Many questions remain around optimal use, stopping and monitoring of treatment in this population. To address these challenges, collaborative research, clinical trials that include people of older ages and patient-centred models of care must be prioritised.
For more information, please see the free online course on ageing well with MS, listen to our podcast episodes on the lived experience of older people with MS and brain health in MS, and the links below.
